title: Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms.
abstract: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease.
authors.affiliation: Unitat de Neuroimmunologia Clínica, CEM-Cat, Hospital Universitari Vall d'Hebron, Barcelona, Spain. mcomabel@ir.vhebron.net
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.forename: David W
authors.initials: DW
authors.lastname: Craig
authors.forename: Montse
authors.initials: M
authors.lastname: Camiña-Tato
authors.forename: Carlos
authors.initials: C
authors.lastname: Morcillo
authors.forename: Cristina
authors.initials: C
authors.lastname: Lopez
authors.forename: Arcadi
authors.initials: A
authors.lastname: Navarro
authors.forename: Jordi
authors.initials: J
authors.lastname: Rio
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
mesh_terms: D002882:Chromosomes, Human, Pair 13; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D009103:Multiple Sclerosis / Q000209:etiology / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens